Relationship between the expression of PD-L1 and 18F-FDG uptake in pancreatic ductal adenocarcinoma.

BACKGROUND: PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses. METHODS: For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18F-FDG PET/CT. Maximum standardised uptake values (SUVmax) were determined. The usefulness of SUVmax for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUVmax of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUVmax was significantly associated with PD-L1 expression in TCs and TIICs (P < 0.001 and P = 0.018, respectively). Using SUVmax cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively. CONCLUSION: Higher 18F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC.

Care readiness and positive feelings of family caregivers of children with liver transplantation in China: A cross-sectional study.

AIM: This research aimed to explore the level of care readiness and positive feelings of family caregivers of children with liver transplantation, and predictive factors of care readiness were alsoinvestigated. BACKGROUND: Children with liver transplant require high level and extensive postoperative care. Family caregivers lack professional care knowledge and experience for surgical trauma, postoperative care, anti rejection drug guidance and so on. Good care readiness can not only promote family caregivers to improve their positive emotions and physical and mental health, but also play a positive role in the recovery of children's diseases. Therefore, efforts are needed to improve the readiness of family caregivers. DESIGN/METHODS: A total of 107 family caregivers of children undergoing liver transplantation participated in this cross-sectional study. Sociodemographic data, disease characteristics, and measures of care readiness and positive feelings were collected using questionnaires.The Care Preparedness Scale (CPS) was used to assess care readiness, and the Positive Aspects of Caregiving (PAC) was used to assess positive feelings of family caregivers of children with liver transplantation. This paper adhered to the STROBE guidelines. RESULTS: According to the statistical results, the total score of the CPS was 18.07 ± 5.51, and that of the PAC was 26.63 ± 4.05. There was a positive correlation between care readiness and positive feelings (r = 0.413, p < 0.05). Multiple linear step-wise regression analysis revealed that the total score of the PAC, undernourishment, caregiver education, relationship with children and care trainingresidence were the independent influencing factors of the readiness of caregivers (p < 0.05). CONCLUSIONS: The care readiness of the family caregivers of children with liver transplantation was at a medium level. Medical personnel can implement targeted health education and carry out personalized care skill training to improve the positive feelings of caregivers and then improve the readiness of caregivers.

Needs for nurses to provide spiritual care and their associated influencing factors among elderly inpatients with stroke in China: A cross-sectional quantitative study.

OBJECTIVES: To investigate the spiritual care needs and associated influencing factors among elderly inpatients with stroke, and to examine the correlations among spiritual care needs, spiritual well-being, self-perceived burden, self-transcendence, and social support. METHODS: A cross-sectional quantitative design was implemented, and the STROBE Checklist was used as the foundation of the study. A convenience sample of 458 elderly inpatients with stroke was selected from three hospitals in China. The sociodemographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Self-Perceived Burden Scale, the Chinese Self-Transcendence Scale, and the Perceived Social Support Scale were used. Descriptive statistics, correlation, Student's t-test, ANOVA, non-parametric, and multiple linear regression analyses were used to analyze the data. RESULTS: The total score of spiritual care needs was 29.82 ± 7.65. Spiritual care needs were positively correlated with spiritual well-being (r = 0.709, p < 0.01), self-transcendence (r = 0.710, p < 0.01), and social support (r = 0.691, p < 0.01), whereas being negatively correlated with self-perceived burden (r = -0.587, p < 0.01). Religious beliefs, educational level, residence place, disease course, spiritual well-being, self-perceived burden, self-transcendence, and social support were found to be the main influencing factors. SIGNIFICANCE OF RESULTS: The spiritual care needs were prevalent and moderate. It is suggested that nurses should enhance spiritual care knowledge and competence, take targeted spiritual care measures according to inpatients' individual personality traits or characteristics and differences of patients, reduce their self-perceived burden and improve their spiritual well-being, self-transcendence and social support in multiple ways and levels, so as to meet their spiritual care needs to the greatest extent and enhance their spiritual comfort.

Abemaciclib is synergistic with doxorubicin in osteosarcoma pre-clinical models via inhibition of CDK4/6-Cyclin D-Rb pathway.

BACKGROUND: Osteosarcoma is a prevalent type of bone tumor in children and adolescents, with limited treatment and poor prognosis. Abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), is approved for the treatment of advanced breast cancer as single agent therapy and is currently under investigation in clinical trials for the treatment of several solid tumors. METHODS: The efficacy of abemaciclib was determined using osteosarcoma cellular assays and xenograft mouse model. The combination studies were performed based on the Chou-Talalay method. Immunoblotting analysis was performed to determine the underlying mechanisms of abemaciclib in osteosarcoma cell lines. RESULTS: Abemaciclib potently inhibits growth, anchorage-independent colony formation and survival of a panel of osteosarcoma cell lines, with IC50 range from 90 nM to >20 µM. In addition, the combination of abemaciclib and doxorubicin is synergistic and antagonistic in abemaciclib-sensitive (IC50 <1 µM) and abemaciclib-resistant (IC50 >1 µM), respectively. Abemaciclib inhibits tumor formation and growth in a dose-dependent manner without causing significant drug toxicity in mice. The combination of abemaciclib and doxorubicin results in much greater efficacy than doxorubicin alone in inhibiting tumor growth throughout the whole treatment duration. Abemaciclib acts on osteosarcoma via suppressing CDK4/6-Cyclin D-Rb pathway. CONCLUSIONS: Our pre-clinical evidence provides a rationale of initializing clinical trial of investigating the efficacy of abemaciclib in combination with doxorubicin in osteosarcoma patients. Our work also highlights the therapeutic value of CDK4/6 inhibition in osteosarcoma with proper function of Rb.